Abstract Human cytomegalovirus (HCMV) is the major viral cause of medical complications associated with bone marrow and organ transplantation. Viral transmission from mother to fetus is implicated in ~15% of stillbirths and ~16,000 birth defects annually in the US. Passive immunization using human immune globulin (HIG) has shown promising activity for both indications. HIG is a complex, variable product that may cause side effects from off-target antibody binding. A monoclonal antibody (mAb) offers qualitative advantages over HIG including potency, safety, production efficiency and quality control. Trellis Bioscience has discovered a high affinity native human mAb (TRL345) against the most conserved site on the HCMV virion (gB AD-2 Site I). This mAb neutralized 15 out of 15 clinical isolates of diverse serotypes. It protected all of the specialized cell types relevant to human pathology. It was also fully protective in a model of the human placenta grown as tissue explants ex vivo. This published work was completed under a Phase I/II SBIR grant. A Master Cell Bank has been developed that expresses TRL345 in CHO cells at a commercially useful level (1.5 g/L) at the 50L fermentor scale. Nearly all IND-enabling analytical work has been completed, including GLP toxicology in rats and tissue reactivity profiling. We now seek CRP funding for developing manufacturing under GMP and for manufacturing material for Phase 1 and 2 human clinical trials. We anticipate initiation of a Phase 1 trial within 6 months after funding, and of a Phase 2 trial within 18 months. Non-grant funding will be used for the actual clinical trial expenses and for manufacturing costs beyond the grant funding level. To support possible extension from the initial transplant indication to the maternal-fetal transmission indication, we propose a non- clinical experimental and regulatory strategy program in year 3 of the grant.